crossing96/oncoscreening huggingface dataset:
Immune response is an important aspect of the antitumor effect produced by a CD40L-encoding oncolytic adenovirus.	Oncolytic adenovirus is an attractive platform for immunotherapy because virus replication is highly immunogenic and not subject to tolerance. Although oncolysis releases tumor epitopes and provides costimulatory danger signals, arming the virus with immunostimulatory molecules can further improve efficacy. CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several immune mechanisms, including a T-helper type 1 (T(H)1) response, which leads to activation of cytotoxic T cells and reduction of immunosuppression. In this study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3-hTERT-E1A-hCD40L)-mediated oncolysis resulted in enhanced calreticulin exposure and HMGB1 and ATP release, which were suggestive of immunogenicity. In two syngeneic mouse models, murine CD40L induced recruitment and activation of antigen-presenting cells, leading to increased interleukin-12 production in splenocytes. This effect was associated with induction of the T(H)1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L also displayed an enhanced presence of macrophages and cytotoxic CD8(+) T cells but not B cells. Together, our findings show that adenoviruses coding for CD40L mediate multiple antitumor effects including oncolysis, apoptosis, induction of T-cell responses, and upregulation of T(H)1 cytokines.	bladder
Factors associated with non-orthotopic urinary diversion after radical cystectomy.	INTRODUCTION: Preoperative factors favoring the performance of non-orthotopic bladder substitution (OBS) after radical cystectomy for muscle-invasive bladder cancer were identified. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 730 patients who underwent radical cystectomy for urothelial carcinoma of the bladder. After excluding 75 patients who were unable to undergo OBS due to the tumor location or elevated serum creatinine level, we assessed the preoperative factors in the remaining 655 patients. Multivariate logistic regression analysis was performed to identify the independent preoperative predictors of type of urinary diversion. RESULTS: Of the 655 patients, 171 (26.1%) underwent non-OBS. Patients who underwent non-OBS were more likely to be older and females, to have a lower educational status, non-organ confined disease, more comorbid medical conditions, more impaired performance status, lower body mass index, anemia, azotemia, and hypoalbuminemia, and to be treated by less-experienced surgeons (P < 0.05 each). After adjusting for provider-based factors, multivariate analysis showed that factors independently associated with non-OBS included advanced age (odds ratio [OR] 4.10, P < 0.001), female gender (OR 2.08, P = 0.027), ECOG performance status (≥ 1 vs 0, OR 5.20, P < 0.001), low educational status (OR 1.59, P = 0.042), clinically node-positive disease (OR 2.36, P = 0.003), anemia (OR 1.67, P = 0.041), azotemia (OR 3.97, P < 0.001), and hypoalbuminemia (OR 1.84, P = 0.046). CONCLUSION: Several patient-based as well as provider-based factors were associated with the type of urinary diversion after radical cystectomy. Advanced age, female gender, low performance status, low education level, clinically node-positive disease, anemia, hypoalbuminemia, and azotemia were associated with non-OBS, as surgery was performed by relatively inexperienced surgeons.	bladder
Characterization and outcomes of small cell carcinoma of the bladder using the surveillance, epidemiology, and end results database.	OBJECTIVE: To utilize the Surveillance, Epidemiology, and End Results Database to analyze clinical features, treatment, and survival outcomes of patients with small cell carcinoma of the bladder in a large population-based sample. Because of its rarity, prior reports are primarily limited to small single-institution studies. METHODS: We identified patients of any age who were diagnosed with small cell carcinoma of the bladder between 1988 and 2007. Kaplan-Meier and Cox regression analysis were used to compare overall survival (OS) and urinary bladder-specific survival. RESULTS: A total of 663 patients were identified. Most patients had either stage II (38.8%) or stage IV (35.4%) disease. The median OS for all patients was 12 months [95% confidence interval (CI), 10.9-13.1]. After excluding those patients who presented with distant metastatic disease or for whom it was unknown whether or not they received any treatment, there were no significant differences in survival between those that received cystectomy (median survival, 21 mo; 95% CI, 14.3-27.7) compared with those who underwent external beam radiation (median survival, 17 mo; 95% CI, 13.4-20.6). On multivariate analysis, both cystectomy (hazard ratio, 0.53; 95% CI, 0.4-0.71; P < 0.001) and radiation (hazard ratio, 0.66; 95% CI, 0.5-0.88; P=0.005) were associated with improved survival. CONCLUSIONS: Small cell carcinoma of the bladder is a rare but aggressive malignancy with poor OS. For those who present without widespread metastatic disease, treatment with either cystectomy or radiation appears to improve survival. Further prospective studies are needed to determine the best approach for treatment of these patients.	bladder
Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes to growth inhibition and apoptosis in human bladder cancer T24 cells.	Ursolic acid (UA) has shown the anti-tumor properties against a number of human cancers both in vivo and in vitro, however, its effect in bladder cancer and the corresponding mechanisms of action remain largely unknown. Here we found that UA dose-dependently induced growth inhibition and apoptosis in human bladder cancer T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to the process. Our Western-blot results demonstrated a significant AMPK activation after UA treatment in T24 cells. Notably, knockdown of AMPKα by the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA's effect. We found the ceramide level was increased after UA treatment in T24 cells, and UA-induced AMPK activation and T24 cell apoptosis were inhibited by ceramide synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell permeable short-chain ceramide (C6), suggesting that ceramide might serve as an upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c-Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1) signaling to cause survivin down-regulation. Our study suggests that activation of AMPK by UA contributes to growth inhibition and apoptosis in human bladder cancer cells.	bladder
Vascular endothelial growth factor, carbonic anhydrase 9, and angiogenin as urinary biomarkers for bladder cancer detection.	OBJECTIVE: To investigate whether elevated urinary levels of vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9), and angiogenin are associated with bladder cancer (BCa). METHODS: This was a case-control study in which voided urine samples from 127 patients (63 control subjects and 64 patients with BCa) were analyzed. The urinary concentrations of VEGF, CA9, angiogenin, and bladder tumor antigen (BTA) were assessed using enzyme-linked immunosorbent assays. We used the area under the curve of receiver operating characteristic curves to determine the ability of VEGF, CA9, and angiogenin to detect BCa in voided urine samples. Data were also compared with the findings from a commercial enzyme-linked immunosorbent assay-based BCa detection assay (BTA-Trak). The sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: The urinary concentrations of VEGF, CA9, angiogenin, and BTA were significantly elevated in those with BCa. VEGF was the most accurate urinary biomarker (area under the curve 0.886, 95% confidence interval 0.8301-0.9418). Furthermore, multivariate regression analysis highlighted VEGF (odds ratio 5.90, 95% confidence interval 2.60-13.40, P < .0001) as an independent variable. The sensitivity and specificity for VEGF (83% sensitivity and 87% specificity) outperformed those for BTA (80% sensitivity and 84% specificity). CONCLUSION: VEGF could be a valuable addition to voided urine sample analysis for the detection of BCa. Larger, prospective studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive evaluation of patients with BCa.	bladder
Sensitivity to chemoradiation predicts development of metastasis in muscle-invasive bladder cancer patients.	OBJECTIVES: In bladder-sparing approaches for muscle-invasive bladder cancer (MIBC) involving transurethral resection of the bladder tumor (TURBT) and chemoradiation, survival outcomes are excellent for patients who achieve tumor-free state after TURBT and chemoradiation but poor for those with persistent disease. Since metastatic disease accounts for most bladder cancer deaths, we hypothesized that tumor sensitivity to chemoradiation may reflect metastatic potential in MIBC. MATERIALS AND METHODS: From 1997 to 2010, 179 cT2-4aN0M0 bladder cancer patients underwent TURBT and induction chemoradiation (40 Gy with cisplatin 20 mg/d for 5 days × 2). Study subjects were 73 patients who had had macroscopic disease after TURBT and were evaluated for tumor sensitivity to the induction chemoradiation; of the 73 patients, chemoradiation response was evaluated pathologically in partial and radical cystectomy specimens for 8 and 44 patients, respectively, and clinically for the remaining 21 who did not undergo cystectomy. Tumors were defined as chemoradiation-sensitive when they regressed to T0 pathologically for the 52 patients undergoing cystectomy or clinically for the 21 undergoing no cystectomy; otherwise, they were defined as chemoradiation-resistant. Primary and secondary endpoints were metastasis-free and cancer-specific survival, respectively. The association between chemoradiation sensitivity and development of metastasis was investigated in MIBC patients. RESULTS: Of the 73 patients, 21 (29%: 13 pathologic and 8 clinical T0) had chemoradiation-sensitive tumors while 52 (71%) had chemoradiation-resistant tumors. Median follow-up was 53 months. Multivariate analysis identified chemoradiation resistance as the strongest independent predictor for the development of metastasis (hazard ratio (HR) 18.9, P < 0.0001). When stratified by chemoradiation sensitivity, 5-year metastasis-free and cancer-specific survival rates were 94.7% and 100%, respectively, for patients with chemoradiation-sensitive tumors, and 45.7% (P = 0.0005) and 41.0% (P < 0.0001), respectively, for patients with chemoradiation-resistant tumors. CONCLUSIONS: Chemoradiation sensitivity predicts the development of metastasis in bladder cancer. Clinical and translational research results indicate that chemoradiation sensitivity is likely to reflect metastatic potential.	bladder
Influence of urinary tract instrumentation and inflammation on the performance of urine markers for the detection of bladder cancer.	OBJECTIVE: To evaluate the impact of inflammation and sampling on cytology, immunocytology, and fluorescence in situ hybridization (FISH) in comparison with NMP22 in hematuria patients. The specificity of urine markers for urothelial cancer is subject to exogenous factors. There is evidence that nuclear matrix protein 22 (NMP22) is influenced by urinary tract infection and instrumented urinary sampling (IUS). METHODS: Samples from 1386 patients with histologic work-up were included. Cytology, immunocytology, FISH, and NMP22-enzyme-linked immunosorbent assay were performed. The presence of inflammation was evaluated by microscopy. The method of urine sampling was recorded in all cases. Any type of urinary tract manipulation was considered as IUS. False-positive results were compared with regard to the presence or absence of inflammation and mechanical manipulation. RESULTS: In all, 1050 (75.7%) patients had no evidence of urothelial cancer. NMP22 results were false positive in 74.3% and 38.4% of patients with and without IUS (P < .0001). False-positive test rates of cytology, immunocytology, and FISH were not increased after manipulation. Inflammation led to a rise in false-positive NMP22 test results (85.3% vs 61.4%, P < .0001). The presence of inflammation did not change the rate of false-positive cytology, immunocytology, and FISH results. CONCLUSION: This is the first study to investigate the impact of inflammation and IUS on cell-based urine markers. In contrast to the protein test NMP22, these factors did not impair the performance of cell-based tests. Hence, patients with positive cytology, immunocytology, and FISH results should undergo diagnostic work-up, even in the case of concomitant inflammation or IUS.	bladder
[Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines].	CONTEXT: New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC with a specific focus on treatment. EVIDENCE ACQUISITION: New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. CONCLUSIONS: In the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.	bladder
Characterization of urine-derived cells from upper urinary tract in patients with bladder cancer.	OBJECTIVE: To investigate whether cells isolated from the upper urinary tract (UTCs) possess stem cell characteristics and could be an alternative cell source for patients with bladder cancer. Current tissue engineering approaches for urologic tissue regeneration require invasive tissue biopsies to obtain autologous cells, and these procedures are associated with potential complications, such as donor site morbidity. Recently, cells isolated from voided urine (VUCs) have been proposed as an alternative cell source for urologic tissue engineering. However, VUCs should not be used in patients with bladder cancer, because the voided urine sample could contain malignant cells. METHODS: Urine samples were collected from the upper urinary tract of 4 male patients with bladder cancer using a ureteral catheter. The samples were centrifuged and the pellets plated for primary culture. The cells were analyzed for colony-forming unit, proliferation rate, cytogenetics, stem cell characterization, and tumorigenicity. The results were compared with those of VUCs collected from 3 healthy men. RESULTS: The UTCs were able to form colonies, had a greater proliferation rate than the VUCs, and had a normal karyotype without any chromosomal aberrations. The UTCs possessed stem cell characteristics (expression of CD44+, CD73+, CD90+, CD105+, SSEA4+) and expressed several markers for urothelial, smooth muscle, and endothelial cell lineages. The UTCs did not form teratoma when implanted into the subcapsular space of a mouse kidney. CONCLUSION: The UTCs possessed stem cell characteristics and can potentially be an alternative cell source for urologic tissue regeneration in patients with bladder cancer.	bladder
Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients.	BACKGROUND: The optimal treatment strategy for muscle-invasive bladder cancer (BCa) remains controversial. OBJECTIVE: Better define the long-term outcomes of radical cystectomy (RC) alone for BCa and determine the impact of pathologic downstaging after transurethral resection in a large and homogeneous single-center series. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 1100 patients undergoing RC with pelvic lymph node dissection (PLND) without neoadjuvant therapy for urothelial carcinoma of the bladder between January 1, 1986, and December 2009 was evaluated. Patients with other than metastases to the pelvic lymph nodes were excluded. Median age was 65 yr. Clinical course, pathologic characteristics, and long-term outcomes were evaluated. Follow-up was obtained until December 2009 with a median of 38 mo and a completeness of 96.5%. INTERVENTION: RC with PLND; urinary diversion with ileal neobladder whenever possible. MEASUREMENTS: Primary end points were disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) according to the tumor stage of the RC specimen versus the maximum tumor stage. The log-rank test was used to compare subgroups. RESULTS AND LIMITATIONS: The 30-d (90-d) mortality rate was 3.2% (5.2%). The 10-yr OS, DSS, and RFS rates were 44.3%, 66.8%, and 65.5%, respectively. Based on the tumor stage of the RC specimen, the 10-yr DSS rate was pT0/a/is/1 pN0: 90.5%, pT2a/b pN0: 66.8%, pT3a/b pN0: 59.7%, pT4a/b pN0: 36.6%, and pTall pN+: 16.7%. Downstaging by transurethral resection of the prostate was observed in 382 patients. Patients with maximum tumor stage pT2a/b pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC specimen: pT2a pN0: 92.2% versus 73.8%; pT2b: 75.0% versus 62.0%. A total of 49% female and 80% male patients received an ileal neobladder. CONCLUSIONS: This contemporary and homogeneous single-center series found acceptable OS, DFS, and RFS for patients undergoing RC. Pathologic downstaging had a significant impact on survival.	bladder
Utility of treatment planning for thermochemotherapy treatment of nonmuscle invasive bladder carcinoma.	"PURPOSE: A recently completed Phase I clinical trial combined concurrent Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of nonmuscle invasive bladder cancer. This work presents a new treatment planning approach, and demonstrates potential impact of this approach on improvement of treatment quality. METHODS: This study retrospectively analyzes a subset of five patients on the trial. For each treatment, expert operators selected ""clinical-optimal"" settings based on simple model calculation on the BSD-2000 control console. Computed tomography (CT) scans acquired prior to treatment were segmented to create finite element patient models for retrospective simulations with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since Sigma-HyperPlan does not account for the convective nature of heat transfer within a fluid filled bladder, an effective thermal conductivity for bladder was introduced. This effective thermal conductivity value was determined by comparing simulation results with clinical measurements of bladder and rectum temperatures. Regions of predicted high temperature in normal tissues were compared with patient complaints during treatment. Treatment results using ""computed-optimal"" settings from the planning system were compared with clinical results using clinical-optimal settings to evaluate potential of treatment improvement by reducing hot spot volume. RESULTS: For all five patients, retrospective treatment planning indicated improved matches between simulated and measured bladder temperatures with increasing effective thermal conductivity. The differences were mostly within 1.3 °C when using an effective thermal conductivity value above 10 W/K/m. Changes in effective bladder thermal conductivity affected surrounding normal tissues within a distance of ∼1.5 cm from the bladder wall. Rectal temperature differences between simulation and measurement were large due to sensitivity to the sampling locations in rectum. The predicted bladder T90 correlated well with single-point bladder temperature measurement. Hot spot locations predicted by the simulation agreed qualitatively with patient complaints during treatment. Furthermore, comparison between the temperature distributions with clinical and computed-optimal settings demonstrated that the computed-optimal settings resulted in substantially reduced hot spot volumes. CONCLUSIONS: Determination of an effective thermal conductivity value for fluid filled bladder was essential for matching simulation and treatment temperatures. Prospectively planning patients using the effective thermal conductivity determined in this work can potentially improve treatment efficacy (compared to manual operator adjustments) by potentially lower discomfort from reduced hot spots in normal tissue."	bladder
Acquired immunogenicity of human DNA damaged by N-hydroxy-N-acetyl-4-aminobiphenyl.	4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study, human placental DNA was modified with N-OH-AABP, and the structural perturbations in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1 digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing female rabbits. The modified DNA was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies, while the native form was almost nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in recognizing various nucleic acid conformers and DNA bases. We also detected deposits of immune complex in glomerular basement membrane in rabbits immunized with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies in cancer patients and the related consequences have been discussed.	bladder